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J Infect Dis. 2015 Jan 1;211(1):10-8. doi: 10.1093/infdis/jiu393. Epub 2014 Jul 16.

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

Author information

1
Toronto General Research Institute, University Health Network.
2
Women's College Research Institute, Women's College Hospital University of Toronto.
3
University of Toronto St. Michael's Hospital.
4
University of Toronto Mount Sinai Hospital, Toronto.
5
Toronto General Research Institute, University Health Network University of Toronto.
6
St. Michael's Hospital.
7
University of Toronto Lakeridge Health, Rouge Valley Hospital, Ajax, Canada.
8
Toronto General Research Institute, University Health Network Women's College Research Institute, Women's College Hospital.

Abstract

BACKGROUND:

Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels.

METHODS:

PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women.

RESULTS:

PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile.

CONCLUSIONS:

Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes.

KEYWORDS:

HIV; lopinavir; low birth weight; pregnancy; progesterone; protease inhibitors; small for gestational age

PMID:
25030058
PMCID:
PMC4264589
DOI:
10.1093/infdis/jiu393
[Indexed for MEDLINE]
Free PMC Article

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